Myelodysplastic syndrome (MDS) and aplastic anemia (AA) share the clinical feature of pancytopenia. However, hematopoiesis is distinct between them; hematopoietic cells are largely but ineffectively produced in the former and little produced in the latter disorder. In addition, urate is the end product of purine nucleotides and is elevated in the serum of patients showing enhanced hematopoiesis. We investigated here whether the production of urate differs between MDS and AA. Serum urate (Sua) and urinary urate excretion (Uua) as well as urate clearance (Cua), creatinine clearance (Ccr), and clearance ratio (Cua/Ccr)were retrospectively determined and were compared among 16 patients with MDS and 26 patients with AA. The values of Sua and Uua were significantly higher in patients with MDS than in those with AA. However, Cua and Cua/Ccr rations were not significantly different. Thus, increase of Sua in those with MDS appeared to be brought about by overproduction of urate in the body, probably by enhanced degradation of purine nucleotides and ineffective erythropoiesis. These findings suggest that Sua and Uua are an index for the differential diagnosis of these two diseases as well as the hematopoietic state in the marrow.

View full abstract

Lesch-Nyhan syndrome (LNS) is caused by a severe genetic deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT). More than 200germline mutations involved in HPRT deficiency have been identified through research in Europe, American and Japan. Most of the mutations (80% or more) are caused by the variety of point mutations located in the HPRT gene (HPRT1). On the other hand, although large genomic alterations account for 20% or less of the mutations, they have not been characterized in detail. By new analysis methods including the Long PCR method, we previously identified at the genomic level an identical large deletion mutation consisting of 2,969 base pairs (bp)expanding from the promoter region to the intron 1 in HPRT1 in two Japanese LNS patients. However, the blood relationship of the patient for two patients was not clarified on a genome level. In order to investigate whether this deletion was a recurrent mutation, we observed whether mitochondrial DNA (mtDNA)and HPRT1 mutations were co-transmitted, and analyzed mtDNA polymorphisms. Consequently, we have confirmed the separate origin of the HPRT1mutation of the two LN patients as assessed with an apparent mtDNA polymorphism. The identical mutation period was reported in Europe, suggesting strongly that Alu-mediated deletion mutation of 2,969by happened at the mutational hot spot of HPRT1.

View full abstract

The effects of long-term use of losartan, an angiotensin II receptor antagonist, on renal handling of uric acid were examined in hyperuricemic patients. The effect was also examined in relation to the type of hyperuricemia and combined use with benzbromarone or allopurinol.38 patients were enrolled in this study. In patients taking 50mg of losartan per day, serum uric acid, uric acid clearance and urinary uric acid excretion were observed over 48 weeks. At 4 weeks, the average level of serum uric acid had decreased from 7.2±1.1mg/dl at baseline to 6.7±1.0mg/dl, and held steady at 6.7±1.1 at 48 weeks. The mechanism by which losartan lowered serum uric acid was considered to be the enhancement of urinary uric acid excretion through the rise of uric acid clearance. Administration of losartan reduced serum uric acid more in patients with underexcretion-type hyperuricemia than overproduction-type hyperuricemia. Losartan also demonstrated a uric acid-lowering effect in an additive fashion in patients already taking benzbromarone or allopurinol. Furthermore, the reduction of uric acid by losartan was stronger in combination with benzbromarone.

View full abstract

Many large-scale cohort studies have indicated that hyperuricemia is an independent risk factor of cardiovascular diseases. Additionally, hypertensive patients frequently exhibit hyperuricemia. In the present study, we investigated the current status of the management of uric acid in 907 hypertensive patients (486 females and 421 males, mean age 66.7±10,8years) who have been treated for at least six months by 34 cardiologists. The percentages of medication and achievement of the target uric acid level were low compared with data for hypertension and hyperlipidemia treatment. When the status was analyzed by the size of facility (Tottori University Hospital, General Hospital, Private practice), the University Hospital was the most successful, and the private practices was the worst. When the status was analyzed by the location of the facility, the percentage of target uric acid achievement in urban areas was better than that in suburban districts. The risk factors of hyperuricemia were male, renal insufficiency, ventricular hypertrophy, prescription of beta-blocker or diureticis and smoking. The management of uric acid of hypertensive patients by cardiologists needs to be improved.

View full abstract